title: CTNNBL1 is a novel nuclear localization sequence-binding protein that recognizes RNA-splicing factors CDC5L and Prp31.
abstract: Nuclear proteins typically contain short stretches of basic amino acids (nuclear localization sequences; NLSs) that bind karyopherin α family members, directing nuclear import. Here, we identify CTNNBL1 (catenin-β-like 1), an armadillo motif-containing nuclear protein that exhibits no detectable primary sequence homology to karyopherin α, as a novel, selective NLS-binding protein. CTNNBL1 (a single-copy gene conserved from fission yeast to man) was previously found associated with Prp19-containing RNA-splicing complexes as well as with the antibody-diversifying enzyme AID. We find that CTNNBL1 association with the Prp19 complex is mediated by recognition of the NLS of the CDC5L component of the complex and show that CTNNBL1 also interacts with Prp31 (another U4/U6.U5 tri-snRNP-associated splicing factor) through its NLS. As with karyopherin αs, CTNNBL1 binds NLSs via its armadillo (ARM) domain, but displays a separate, more selective NLS binding specificity. Furthermore, the CTNNBL1/AID interaction depends on amino acids forming the AID conformational NLS with CTNNBL1-deficient cells showing a partial defect in AID nuclear accumulation. However, in further contrast to karyopherin αs, the CTNNBL1 N-terminal region itself binds karyopherin αs (rather than karyopherin β), suggesting a function divergent from canonical nuclear transport. Thus, CTNNBL1 is a novel NLS-binding protein, distinct from karyopherin αs, with the results suggesting a possible role in the selective intranuclear targeting or interactions of some splicing-associated complexes.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, United Kingdom.
authors.forename: Karuna
authors.initials: K
authors.lastname: Ganesh
authors.forename: Salome
authors.initials: S
authors.lastname: Adam
authors.forename: Benjamin
authors.initials: B
authors.lastname: Taylor
authors.forename: Paul
authors.initials: P
authors.lastname: Simpson
authors.forename: Cristina
authors.initials: C
authors.lastname: Rada
authors.forename: Michael
authors.initials: M
authors.lastname: Neuberger
mesh_terms: D021581:Active Transport, Cell Nucleus; D017398:Alternative Splicing; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D018797:Cell Cycle Proteins / Q000737:chemistry*; D005136:Eye Proteins / Q000737:chemistry*; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D019913:Nuclear Localization Signals / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry*; D040901:Proteomics; D016601:RNA-Binding Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D028901:alpha Karyopherins / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C508357:CDC5L protein, human; C479429:CTNNBL1 protein, human; D018797:Cell Cycle Proteins; D005136:Eye Proteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; C454222:PRPF31 protein, human; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D028901:alpha Karyopherins; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase